We have examined the control of membrane protein phosphorylation in the human erythrocyte. In intact erythrocytes, the major phosphopeptide is Band II, a component of spectrin. The enzyme mediating this phosphorylation is a cyclic AMP independent protein kinase, which partitions between the cytoplasm and the plasma membrane. The membrane also contains a cyclic AMP dependent protein kinase which mediates the phosphorylation of a large number of membrane peptides, both in intact cells and isolated membranes. Erythrocytes also contain an inactive protein phosphatase, which is virtually entirely cytoplasmic in location. This enzyme avidly dephosphorylates P32 spectrin (Band II) in solution and appears to be under metabolic regulation. Studies are currently directed at the isolation and purification of the kinases and phospatase; characterization of the phosphorylated substrate; studies in intact cells defining the effects of external stimuli and the internal milieu on the state of erythrocyte membrane protein phosphorylation.